The pharmacokinetics of deuterium-labeled cocaine and methamphetamine in hair, skin, sweat, and sebum, and plasma will be characterized so as to better understand mechanisms by which drugs enter hair. Skin and its secretions as possible reservoirs and transport vehicles for drugs will be considered. Dose-dependent concentrations, time-course of uptake and disappearance, and relationships between the skin concentrations of drugs and major metabolites in various biofluid and tissue samples will be determined. The significance of sweat and sebaceous-gland secretions, hair color, and racial differences as determinants of uptake of drugs into hair will be determined. Sequential plasma, urine, skin, sweat, and hair samples will be analyzed by gas chromatography and mass spectrometry. Drug concentrations will be measured in skin-punch biopsy specimens, stratum corneum, interstitial fluid, sebum, sweat, and hair. Relationships between dose and the skin concentrations, skin pharmacological responses, and hair levels will be determined. The use of isotope-labeled drugs will allow many months of outpatient study after a single laboratory dose, since illicit use of the test drug will not interfere with following the course of the labeled test dose. The research will provide useful scientific information for interpretation of hair and sweat and hair analysis as a biomarker for exposure to drugs and chemicals. GCRC will allow for precise timed sample collection and processing, control of any illicit drug exposure, and close observation of volunteer subjects, increasing their safety and enhancing the quality of data collected.